| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 5917406 | Molecular Immunology | 2012 | 10 Pages |
Cytokines produced by inflammatory or resident mesenchymal cells play important modulatory roles in the pathogenesis of inflammation induced bone loss. In the present study, the effects of IL-4 and IL-13 on the expression of three osteotropic cytokines in the IL-6 family expressed in human gingival fibroblasts were studied. IL-4Rα and IL-13Rα1 mRNA were constitutively expressed in human gingival fibroblasts. The inflammatory cytokines IL-1β and TNF-α increased expression of IL-6, LIF, and IL-11 mRNA and protein in the gingival fibroblasts. Addition of IL-4 or IL-13 had no effect on IL-6 expression, but significantly inhibited LIF and IL-11 mRNA and protein stimulated by IL-1β and TNF-α. No involvement of NF-κB or STAT1 was observed in the inhibition. STAT6 was phosphorylated at Y641 by treatment with IL-4 and knockdown of STAT6 with siRNA decreased the inhibition of IL-11 and LIF expression by IL-4 in IL-1β and TNF-α stimulated cells. This study suggests that activation of STAT6 by IL-4 and IL-13, through type 2 IL-4 receptors, inhibits production of IL-11 and LIF stimulated by IL-1β and TNF-α in human gingival fibroblasts. A negative modulatory role of IL-4 and IL-13 in osteotropic cytokine production could be a mechanism playing an important inhibitory role in inflammation induced periodontitis.
⺠We examined the effects of IL-4 and IL-13 on the expression of IL-6, IL-11 and LIF. ⺠IL-4 or IL-13 had no effect on IL-6 expression. ⺠IL-4 and IL-13 inhibit LIF and IL-11 mRNA and protein stimulated by IL-1β and TNF-α. ⺠STAT6 is involved in the inhibition, but not STAT1 or NFκB.
